Long-Term Follow-Up of Patients with 46,XY Partial Gonadal Dysgenesis Reared as Males

Juliana Gabriel Ribeiro De Andrade,Andréa Trevas Maciel-Guerra,Antonia Paula Marques-De-Faria,Gil Guerra-Júnior,Helena Campos Fabbri,Maricilda Palandi De Mello

doi:10.1155/2014/480724

Juliana Gabriel Ribeiro De Andrade, Andréa Trevas Maciel-Guerra + Show 4 more

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https://doi.org/10.1155/2014/480724

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Abstract

Background/Aims. Studies on 46,XY partial gonadal dysgenesis (PGD) have focused on molecular, gonadal, genital, and hormone features; little is known about follow-up. Our aim was to analyze long-term outcomes of PGD. Methods. Retrospective longitudinal study conducted at a reference service in Brazil. Ten patients were first evaluated in the 1990s and followed up until the 2010s; follow-up ranged from 13.5 to 19.7 years. All were reared as males and had at least one scrotal testis; two bore NR5A1 mutations. Main outcomes were: associated conditions, pubertal development, and growth. Results. All patients had normal motor development but three presented cognitive impairment; five had various associated conditions. At the end of the prepubertal period, FSH was high or high-normal in 3/6 patients; LH was normal in all. At the last evaluation, FSH was high or high-normal in 8/10; LH was high or high-normal in 5/10; testosterone was decreased in one. Final height in nine cases ranged from −1.57 to 0.80 SDS. All had spontaneous puberty; only one needed androgen therapy. Conclusions. There is good prognosis for growth and spontaneous pubertal development but not for fertility. Though additional studies are required, screening for learning disabilities is advisable.

Highlights

Partial gonadal dysgenesis (PGD), one of the 46,XY disorders of sex development (DSD) [1], is a rare disorder characterized by sex ambiguity due to variable degrees of testicular dysgenesis in individuals without a syndromic picture who have a normal male karyotype
PGD was initially considered by many authors as a variant of 46,XY complete gonadal dysgenesis (CGD), which is characterized by bilateral streak gonads and female internal and external genitalia
Our results showed that all patients had normal neuromotor development, that most had normal growth, and that there was no consistent pattern of associated conditions

Summary

Introduction

Partial gonadal dysgenesis (PGD), one of the 46,XY disorders of sex development (DSD) [1], is a rare disorder characterized by sex ambiguity due to variable degrees of testicular dysgenesis in individuals without a syndromic picture who have a normal male karyotype.The histology of dysgenetic testes may vary from gonads with a few tubular structures and predominance of fibrous tissue to those with mild abnormalities, such as reduction of mean tubular diameter and mean number of germ cells and Sertoli cells per tubular profile [2]. Dysgenetic testes may be found bilaterally or may be associated with streak gonads, and the degree of embryonic Sertoli and Leydig cell dysfunction determines the degree of virilization of the internal and external genitalia [2]. PGD was initially considered by many authors as a variant of 46,XY complete gonadal dysgenesis (CGD), which is characterized by bilateral streak gonads and female internal and external genitalia. Mutations in SRY (sex determining region Y) gene, which have been described in many cases of XY CGD [6, 7], are rarely seen in PGD [8,9,10] In recent years, both heterozygous and homozygous mutations in NR5A1 (Nuclear Receptor Subfamily 5, Group A, Member 1) gene, which codifies the SF1 (steroidogenic factor 1)

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